1. Field of the Invention
This invention relates to a medical diagnostic device that includes an element for controlling fluid flow through the device; more particularly, to a device that facilitates fluid flow through a stop junction.
2. Description of the Related Art
A variety of medical diagnostic procedures involve tests on biological fluids, such as blood, urine, or saliva, to determine an analyte concentration in the fluid. The procedures measure a variety of physical parametersxe2x80x94mechanical, optical, electrical, etc.,xe2x80x94of the biological fluid.
Among the analytes of greatest interest is glucose, and dry phase reagent strips incorporating enzyme-based compositions are used extensively in clinical laboratories, physicians"" offices, hospitals, and homes to test samples of biological fluids for glucose concentration. In fact, reagent strips have become an everyday necessity for many of the nation""s estimated 16 people with diabetes. Since diabetes can cause dangerous anomalies in blood chemistry, it can contribute to vision loss, kidney failure, and other serious medical consequences. To minimize the risk of these consequences, most people with diabetes must test themselves periodically, then adjust their glucose concentration accordingly, for instance, through diet, exercise, and/or insulin injections. Some patients must test their blood glucose concentration as often as four times or more daily.
One type of glucose measurement system operates electrochemically, detecting the oxidation of blood glucose on a dry reagent strip. The reagent generally includes an enzyme, such as glucose oxidase or glucose dehydrogenase, and a redox mediator, such as ferrocene or ferricyanide. This type of measurement system is described in U.S. Pat. No. 4,224,125, issued on Sep. 23, 1980, to Nakamura et al.; and U.S. Pat. No. 4,545,382, issued on Oct. 8, 1985, to Higgins et al., incorporated herein by reference.
Hodges et al., WO 9718464 A1, published on May 22, 1997, discloses an electrochemical device for measuring blood glucose that includes two metallized polyethylene terephthalate (PET) layers sandwiching an adhesive-coated PET intermediate layer. The metallized layers constitute first and second electrodes, and a cutout in the adhesive-coated layer defines an electrochemical cell. The cell contains the reagent that reacts with the glucose in a blood sample. The device is elongated, and the sample is introduced at an inlet on one of the long sides.
The electrochemical devices for measuring blood glucose that are described in the patents cited above, as well as other medical diagnostic devices used for measuring analyte concentrations or characteristics of biological fluids, generally share a need to transport the fluid from a sample inlet to one or more other sections of the device. Typically, a sample flows through capillary channels between two spaced-apart surfaces. A number of patents, discussed below, disclose medical diagnostic devices and include descriptions of various methods to control the flow of the sample.
U.S. Pat. No. 4,254,083, issued on Mar. 3, 1981, to Columbus, discloses a device that includes a sample inlet configured to facilitate movement of a drop of fluid sample into the device, by causing a compound meniscus to form on the drop. (See also U.S. Pat. No. 5,997,817, issued on Dec. 7, 1999 to Crismore et al.)
U.S. Pat. No. 4,426,451, issued on Jan. 17, 1984 to Columbus, discloses a multi-zone fluidic device that has pressure-actuatable means for controlling the flow of fluid between the zones. His device makes use of pressure balances on a liquid meniscus at the interface between a first zone and a second zone that has a different cross section. When both the first and second zones are at atmospheric pressure, surface tension creates a back pressure that stops the liquid meniscus from proceeding from the first zone to the second. The configuration of this interface or xe2x80x9cstop junctionxe2x80x9d is such that the liquid flows into the second zone only upon application of an externally generated pressure to the liquid in the first zone that is sufficient to push the meniscus into the second zone.
U.S. Pat. No. 4,868,129, issued on Sept. 19, 1989 to Gibbons et al., discloses that the back pressure in a stop junction can be overcome by hydrostatic pressure on the liquid in the first zone, for example by having a column of fluid in the first zone.
U.S. Pat. No. 5,230,866, issued on Jul. 27, 1993 to Shartle et al., discloses a fluidic device with multiple stop junctions in which the surface tension-induced back pressure at the stop junction is augmented; for example, by trapping and compressing gas in the second zone. The compressed gas can then be vented before applying additional hydrostatic pressure to the first zone to cause fluid to flow into the second zone. By varying the back pressure of multiple stop junctions in parallel, xe2x80x9crupture junctionsxe2x80x9d can be formed, having lower maximum back pressure.
U.S. Pat. No. 5,472,603, issued on Dec. 5, 1995 to Schembri (see also U.S. Pat. No. 5,627,041), discloses using centrifugal force to overcome the back pressure in a stop junction. When flow stops, the first zone is at atmospheric pressure plus a centrifugally generated pressure that is less than the pressure required to overcome the back pressure. The second zone is at atmospheric pressure. To resume flow, additional centrifugal pressure is applied to the first zone, overcoming the meniscus back pressure. The second zone remains at atmospheric pressure.
U.S. Pat. No. 6,011,307, issued on Dec. 14, 1999, to Naka et al., published on Oct. 29, 1997, discloses a device and method for analyzing a sample that includes drawing the sample into the device by suction, then reacting the sample with a reagent in an analytical section. Analysis is done by optical or electrochemical means. In alternate embodiments, there are multiple analytical sections and/or a bypass channel. The flow among these sections is balanced without using stop junctions.
U.S. Pat. No. 5,700,695, issued on Dec. 23, 1997 to Yassinzadeh et al., discloses an apparatus for collecting and manipulating a biological fluid that.uses a xe2x80x9cthermal pressure chamberxe2x80x9d to provide the driving force for moving the sample through the apparatus.
U.S. Pat. No. 5,736,404, issued on Apr. 7, 1998, to Yassinzadeh et al., discloses a method for determining the coagulation time of a blood sample that involves causing an end of the sample to oscillate within a passageway. The oscillating motion is caused by alternately increasing and decreasing the pressure on the sample.
None of the references discussed above suggest a device in which a flow channel has a stop junction that is angular in the flow direction.
This invention provides a medical diagnostic device for measuring an analyte concentration in a biological fluid. The device comprises a capillary flow channel within the device, in fluid communication with a sample inlet, the flow channel
a) adapted for conveying a sample of the biological fluid in a first direction, from a first region, proximate to the sample inlet, to a second region, distal to the sample inlet, the first region having a capillary dimension in a second direction, substantially perpendicular to the first direction; and
b) having a stop junction, comprising a boundary region that
i) separates the first and second regions,
ii) has a predetermined dimension in the second direction that is greater than the capillary dimension, and
iii) forms an angle that points toward the first region.
Note that in the present specification and the figures, capillaries are shown bounded by parallel plates. In that case, the xe2x80x9csecond directionxe2x80x9d, which has the capillary dimension, is uniquely determined. Alternatively, capillaries of the invention could be cylindrical. In that case, the second direction is radial, in a planar circle, or disk, that is perpendicular to the direction of fluid flow.
Devices of the present invention provide, in a flow channel of the device, a stop junction that is angular in the flow direction. Such a stop junction can be designed with readily-controlled break-through pressure.